Arthritis is a disorder accompanied by joint stiffness and continuous periarticular pains caused by one or more joint inflammations. Arthritis can be classified into an acute arthritis and a chronic arthritis. The chronic arthritis such as gouty arthritis, polyarthritis, rheumatoid arthritis and osteoarthritis deformans caused by aging of bones or joints results in continuous periarticular pains.
Rheumatoid arthritis among the chronic arthritis is a chronic inflammatory disorder of unknown cause characterized by polyarthritis. The exact cause of the rheumatoid arthritis has not been known up to date. But, it has been generally considered that a hereditary tendency, bacterial or viral infections and the likes induce the rheumatoid arthritis to develop and inferred that hormones are concerned in developing the rheumatoid arthritis. The rheumatoid arthritis has harmful influences on not only joints but also other organs of the body. Accordingly, patients who have induced rheumatoid arthritis cannot walk and use their own hands or feet, and frequently feel tired or unpleasant. Furthermore, rheumatoid arthritis cause weight loss, lack of sleep and the likes, and continuous rheumatoid arthritis results in limitation of physical activity of the patients caused by muscular weakening, and thereby, considerably influencing on private and social activities of the patients. Also, when the physical activity of the patients is limited caused by rheumatoid arthritis, it is highly likely that the patients become obese and suffer from heart disease resulted from high cholesterol level and get the blues.
Rheumatoid arthritis has been occurred 0.2 cases for every 1,000 people for men and 0.4 cases per 1,000 persons for women per year, and prevalence of rheumatoid arthritis is 0.4-1.4%, which shows relatively even distribution in worldwide. As the aging population has increased gradually, it is expected that the market of therapeutic agents for rheumatoid arthritis grow sharply.
Currently, non-steroidal anti-inflammatory drugs (NSAID); steroids; non-biological disease-modifying anti-rheumatoid drugs (DMARD) such as anti-malarial drugs, hydroxychloroquinone (HCQ), sulfasalazine, methotrexate (MTX), leflunomide; and biological anti-rheumatoid drugs such as tumor necrosis factor (TNF) inhibitors or IL-6 inhibitors have been used as therapeutic agents for rheumatoid arthritis.
As the biological anti-rheumatoid drugs, tumor necrosis factor (TNE) inhibitors such as etanercept, adalimumab, infliximab, golimumab and certolizumab; monoclonal antibody Rituximab as a B-cell inhibitor; Abatacept blocking immune responses between antigen-presenting cells and T-cell; Tofacitinib blocking selectively JAK (Janus activated kinase) as a small molecule inhibitor and the likes have been developed.
But, most of those therapeutic agents for rheumatoid arthritis induce severe side effects. For example, non-steroidal anti-inflammatory drugs have caused gastrointestinal side effects, and some non-steroidal anti-inflammatory drugs including selective COX-2 inhibitors may induce severe side effects in cardiovascular system. Besides, it has been known that non-steroidal anti-inflammatory drugs induce side effects such as decline in renal function, interstitial nephritis, an acute renal failure and the likes. When administering steroids for a long term, they cause atrophy of hypothalamus-pituitary gland-adrenal gland so that adrenal insufficiency may be occurred, and they induce other side effects such as glaucoma, cataract, osteonecrosis, osteoporosis, hypertension, hypokalemia, and the likes. Particularly, because the non-steroidal anti-inflammatory drugs and steroids do not suppress of the progression of arthritis in reality, but only alleviates inflammation, they show little effects with regard to preventing joint damages.
Meanwhile, currently developed anti-rheumatoid drugs can suppress of the progression of early rheumatoid arthritis, but they cannot cure completely rheumatoid arthritis. Also, it has been reported that anti-rheumatoid drugs can induce some side effects. For example, some non-biological anti-rheumatoid drugs can induce side effects such as visual disturbance, retinopathy, skin rash, hepatic dysfunction, nausea and the likes. Also, tumor necrosis factor inhibitors of biological anti-rheumatoid drugs have problems such as blood abnormality, heart failure, hepatic dysfunction and opportunistic infection and IL-6 inhibitors can cause side effects such as hepatic dysfunction, leucopenia and the likes. It has been reported that other biological anti-rheumatoid drugs can induce infection problems as well as side effects such as a risk of tumorigenesis, gastrointestinal perforation and hyperlipidemia.
Particularly, most of the biological anti-rheumatoid drugs have a fatal defect that they can be administered only through subcutaneous injection or intravascular injection, and induce response decline to the drugs owing to immunogenicity by the human body by lapse of time. Also, since the currently developed biological anti-rheumatoid drugs suppress general immune system, they are exposed to the vulnerability of opportunistic infections and cancer suppression. Furthermore, those biological anti-rheumatoid drugs are very expensive, which causes financial burdens of patients considerably. Particularly, not a few patients with rheumatoid arthritis do no react to monoclonal antibodies which have been used as a representative biological anti-rheumatoid drug.